Hydro-alcoholic fruit extract of Cordia myxa was considerably effective on curing acute inflammation in mouse\nmodel. Previous studies suggested significant anti-inflammatory activities as well as potential anticancer agent of\n-amyrins in seeds. Inhibition of Cyclooxygenase-2 (COX-2) and 5-Lipooxygenase (5-LOX) is significant in\ncancer prevention and therapeutics although this inhibition with chemo-drugs has its own side-effects. It is\nshown that these enzymes pathways are related to several cancers including colon, breast and lung cancer. This\nstudy was conducted based on Cordia species� -amyrins as a safer natural anti-cancer compound for inhibition\nof COX-2 and 5-LOX enzymes by molecular docking. The X-ray crystal structure of COX2 / 5-LOX enzymes\nand -amyrins was retrieved and energetically minimized respectively. The binding site and surface of enzymes\nwere detected. Docking studies were performed by AutoDock 4.2 using Lamarckian genetic algorithm (LGA).\nFinally drug likeness, molecular pharmacokinetic properties and toxicity of -amyrins was calculated. Molecular\nDocking revealed hydrogen and hydrophobic interactions between -amyrins with both active sites of COX-2\nand 5-LOX enzymes. Interestingly, it covalently bonded to Fe cofactor of 5-LOX enzyme and chelated this molecule.\nBase on binding energies (G) -amyrin has more inhibitory effects on 5-LOX (-10.45 Kcal/mol) than\nCOX-2 (-8.02 Kcal/mol). Analysis of molecular pharmacokinetic parameters suggested that -amyrins complied\nwith most sets of Lipinski's rules, and so it could be a suitable ligand for docking studies. Eventually, bioactivity\nscore showed -amyrins possess considerable biological activities as nuclear receptor, enzyme inhibitor, GPCR\nand protease inhibitor ligand. These results clearly demonstrate that -amyrins could act as potential highly selective\nCOX-/5-LOX inhibitor. Also, it is a safe compound in comparison with classical non-steroidal antiinflammatory\ndrugs (NSAIDs) that are known as cancer preventive agents, since it is free of side effects on human\nbody and it can be a promising drug for cancer therapeutics.
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